Over the next 5 years my career goals include (1) conducting original research on the epidemiology and impact of metabolic complications of HIV disease, (2) developing a comprehensive program to mentor trainees with career interests in patient-oriented research, (3) the expansion of my research program to include an international component. The rich diversity of ongoing basic and clinical research on HIV infection at UCLA and the facilities available in the Center for Clinical AIDS Research and Education provide tremendous resources to enhance my experience as a clinical investigator and provide a stimulating atmosphere for my trainees. The K24 Award will help me to achieve my career goals by providing me with a significant amount of protected time to devote to mentoring my trainees, gaining additional training for myself in biostatistics and focusing on my own research program. This application describes a comprehensive training program for fellows, which includes formal training in biostatistics and clinical research methods. In addition four research projects are described. The proposed research will investigate the natural history of insulin resistance among a cohort of well-characterized patients on long term HAART and examine in detail gender differences in prevalence of insulin resistance and lipid abnormalities in men and women enrolled in a cross-sectional study of metabolic complications. A prospective, matched, cohort study will compare measurements of carotid intima medial thickness between patients with HIV infection treated with a protease inhibitor or no therapy to patients without HIV infection in order to test the hypothesis that protease inhibitor therapy is associated with an increased risk of subclinical atherosclerosis. A randomized clinical trial comparing three antiretroviral regimens among subjects enrolled at twelve sites located in resource poor settings around the world will provide the opportunity to examine the factors associated with the development of immune reconstitution syndromes and to determine whether these syndromes predict an altered response to HAART. The strong support from my Division Chief and Department Chair to allow me to reduce my clinical and administrative responsibilities will greatly facilitate my success in achieving my goals.